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In Joseph Moncure March's narrative poem, which was the inspiration for this film, the protagonist boxer is a black man. According to modern sources, African-American actor James Edwards (1918-1970) was first slated to star in the picture as late as the fall of 1948, but was eventually replaced by Robert Ryan. Edwards, who made his motion picture debut in The Set-Up, appears as boxer "Luther Hawkins." In March 1947, Shepard Traube was announced in Hollywood Reporter as the film's director. On June 30, 1948, Dore Schary resigned his post as RKO production head, citing new studio owner Howard Hughes's decision to shelve The Set-Up and two other projects as the primary reason for his departure. By the end of July 1948, The Set-Up was back on the RKO production schedule and was to be the first picture made on Hughes's new "modified production program." While he was a student at Dartmouth University, star Robert Ryan was an undefeated boxing champion. Former boxing professional John Indrisano, who is credited onscreen for "fighting sequences," coached Ryan for the production. Hal Fieberling, who plays "Tiger Nelson" in the picture, was also an expert boxer, according to Los Angeles Times.
When filming began in mid-October 1948, the part of "Julie" had yet to be cast, according to Hollywood Reporter. RKO eventually borrowed Audrey Totter from M-G-M for the picture. Although a Hollywood Reporter news item claimed that Totter's part was the only woman's role in the picture, several other actresses appear in the film. A New York Times article claimed that Totter's wardrobe cost $5.95. Arthur Weegee Fellig, who plays a timekeeper in the picture, was a well-known news photographer known as "Weegee," according to Hollywood Reporter. The film was somewhat unusual in that narrative time and screen time are the same-seventy-two minutes. (Publicity for The Set-Up states that the film "covers 80 minutes, second-by-second of a ring-scarred bruiser's life," and adds that "incidents are filmed exactly as they happened, and in accurate chronological order.") In addition, no musical score was written for the picture; all the music presented is music heard by the characters within the scenes.
Hollywood Reporter news items report that just before the picture's release, RKO filed a $500,000 lawsuit against Screen Plays Pictures, charging it with copyright infringement in connection with its production Champion . RKO tried unsuccesfully to secure a federal restraining order against the opening of Champion, a boxing drama starring Kirk Douglas. After several court delays, Judge Pierson M. Hall viewed both films and ruled that, while the majority of Champion was wholly original, a few scenes were very similar to ones in The Set-Up. He ordered that both RKO and Screen Plays recut the scenes in question and then dismissed the lawsuit. According to Hollywood Reporter, less than one minute of footage in Champion and two words of dialogue were changed.
Many reviewers commented on the stark and critical view of boxing presented in The Set-Up. The New York Times review commented: "The sweaty, stale-smoke atmosphere of an ill-ventilated small-time arena and the ringside types who work themselves into a savage frenzy have been put on the screen in harsh, realistic terms." The Set-Up is often cited by modern critics as one of the most influential boxing films of its time. In a modern interview, Ryan cited his role in The Set-Up as his favorite. Director Robert Wise won the Critic's Prize at the Cannes Film Festival for his work on the picture. The Set-Up was his last film for RKO. In 2002, RKO announced a remake of The Set-Up; as of spring 2005, Franc Reyes was attached as the director, but the film had not yet gone into production.